The interferons (IFNs) have been classified into two distinct groups: type I interferons, including IFN.alpha., IFN.beta., IFN.tau., and IFN.omega. (also known as IFN.alpha.II); and type II interferons, represented by IFN.gamma. (reviewed by DeMaeyer, et al., 1988). In humans, it is estimated that there are at least 17 IFN.alpha. non-allelic genes, at least 2 IFN.beta. non-allelic genes, and a single IFN.gamma. gene.
IFN.alpha.'s have been shown to inhibit various types of cellular proliferation. IFN.alpha.'s are especially useful against hematologic malignancies such as hairy-cell leukemia (Quesada, et al., 1984). Further, these proteins have also shown activity against multiple myeloma, chronic lymphocytic leukemia, low-grade lymphoma, Kaposi's sarcoma, chronic myelogenous leukemia, renal-cell carcinoma, urinary bladder tumors and ovarian cancers (Bonnem, et al., 1984; Oldham, 1985). The role of interferons and interferon receptors in the pathogenesis of certain autoimmune and inflammatory diseases has also been investigated (Benoit, et al., 1993).
IFN.alpha.'s are also useful against various types of viral infections (Finter, et al., 1991). Alpha interferons have shown activity against human papillomavirus infection, Hepatitis B, and Hepatitis C infections (Finter, et al., 1991; Kashima, et al., 1988; Dusheiko, et al., 1986; Davis, et al., 1989).
Significantly, however, the usefulness of IFN.alpha.'s has been limited by their toxicity: use of interferons in the treatment of cancer and viral disease results in serious side effects, such as fever, chills, anorexia, weight loss, and fatigue (Pontzer, et al., 1991; Oldham, 1985). These side effects often require (i) the interferon dosage to be reduced to levels that limit the effectiveness of treatment, or (ii) the removal of the patient from treatment. Such toxicity has reduced the usefulness of these potent antiviral and antiproliferative proteins in the treatment of debilitating human and animal diseases.